Small interfering RNAs and methods for prevention, inhibition and/or treatment of malignant progression of breast cancer

Abstract

The invention found that overexpression and activation of α9-nAChR are associated with tumorigenesis of breast cancer and create a number of small interfering RNAs to inhibit the expression of α9-nAChR so as to inhibit breast cancer. Therefore, the invention provides small interfering RNAs (siRNAs) for inhibiting expression of α9-nAChR so as to inhibit breast cancer, methods to prevent/inhibit/treat malignant progression of nicotine-derived-compound-induced breast cancer and method of determining malignant level of such breast cancer.

1. An siRNA molecule for suppressing expression of α9-nAChR gene via RNA interference (RNAi), which comprises: a sense strand having at least the sequence of SEQ ID NO: 1 or SEQ ID NO: 3 or a complementary sequence thereof having sufficient complementarity to an RNA of said α9-nAChR gene for the siRNA molecule to direct cleavage of said RNA via RNA interference. 
     
     
       2. The siRNA molecule of  claim 1 , wherein the complementary sequence has 70%, 80%, 90%, or 100% complementary to SEQ ID NO: 1 or SEQ ID NO:3. 
     
     
       3. The siRNA molecule of  claim 1 , wherein the complementary sequence has the sequences as shown in SEQ ID NO: 2 that is perfectly complementary to SEQ ID NO: 1 and SEQ ID NO: 4 that is perfectly complementary to SEQ ID NO: 3. 
     
     
       4. The siRNA molecule of  claim 1 , which is a sequence further comprising a hairpin loop region and a sequence complementary to SEQ ID NO: 1 or SEQ ID NO: 3, or a complementary sequence thereof having sufficient complementarity to an RNA of said α9-nAChR gene for the siRNA molecule to direct cleavage of said RNA via RNA interference. 
     
     
       5. The siRNA molecule of  claim 4 , which can be in linear for hairpin form. 
     
     
       6. The siRNA molecule of  claim 4 , wherein the hairpin loop region has 5, 6, 7, 8, 9, 10, 11, 12 or 13 nucleotides in length. 
     
     
       7. The siRNA molecule of  claim 4 , wherein the hairpin loop region is the sequence of TTCAAGAGA (SEQ ID NO:9) or TCTCTTGAA (SEQ ID NO:10). 
     
     
       8. The siRNA molecule of  claim 4 , which comprises the sequence as shown in SEQ ID NO: 5 and SEQ ID NO: 7. 
     
     
       9. The siRNA molecule of  claim 4 , wherein the complementary sequence has the sequences as shown in SEQ ID NO: 6 that is perfectly complementary to SEQ ID NO: 5 and SEQ ID NO: 8 that is perfectly complementary to SEQ ID NO: 7. 
     
     
       10. A pharmaceutical composition comprising a siRNA molecule of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       11. A method of inhibiting and/or treating malignant progression of nicotine-derived-compound-induced breast cancer, comprising administering to a subject an α9-nAChR inhibitor in an amount effective to reduce α9-nAChR expression, wherein the α9-nAChR inhibitor is the siRNA molecule of  claim 1 , thereby treating and/or inhibiting and/or treating malignant progression of said breast cancer. 
     
     
       12. The method of  claim 11 , wherein the α9-nAChR inhibitor is administrated via oral, inhaled, buccal, parenteral, transdermal and routes or with a liposome. 
     
     
       13. The method of  claim 11 , wherein the dosage amounts of the α9-nAChR inhibitor ranges from 10 mg/kg/day to 500 mg/kg/day.